Combining epidemiology with basic biology of sand flies, parasites, and hosts to inform leishmaniasis transmission dynamics and control.

Quantitation of the nonlinear heterogeneities in Leishmania parasites, sand fly vectors, and mammalian host relationships provides insights to better understand leishmanial transmission epidemiology towards improving its control. The parasite manipulates the sand fly via production of promastigote secretory gel (PSG), leading to the "blocked sand fly" phenotype, persistent feeding attempts, and feeding on multiple hosts. PSG is injected into the mammalian host with the parasite and promotes the establishment of infection. Animal models demonstrate that sand flies with the highest parasite loads and percent metacyclic promastigotes transmit more parasites with greater frequency, resulting in higher load infections that are more likely to be both symptomatic and efficient reservoirs. The existence of mammalian and sand fly "super-spreaders" provides a biological basis for the spatial and temporal clustering of clinical leishmanial disease. Sand fly blood-feeding behavior will determine the efficacies of indoor residual spraying, topical insecticides, and bed nets. Interventions need to have sufficient coverage to include transmission hot spots, especially in the absence of field tools to assess infectiousness. Interventions that reduce sand fly densities in the absence of elimination could have negative consequences, for example, by interfering with partial immunity conferred by exposure to sand fly saliva. A deeper understanding of both sand fly and host biology and behavior is essential to ensuring effectiveness of vector interventions

Both Trait and State Mindfulness Predict Lower Aggressiveness via Anger Rumination: a Multilevel Mediation Analysis

Trait mindfulness, or the capacity for nonjudgmental, present-centered attention, predicts lower aggression in cross-sectional samples, an effect mediated by reduced anger rumination. Experimental work also implicates state mindfulness (i.e., fluctuations around one's typical mindfulness) in aggression. Despite evidence that both trait and state mindfulness predict lower aggression, their relative impact and their mechanisms remain unclear. Higher trait mindfulness and state increases in mindfulness facets may reduce aggression-related outcomes by (1) limiting the intensity of anger, or (2) limiting rumination on anger experiences. The present study tests two hypotheses: First, that both trait and state mindfulness contribute unique variance to lower aggressiveness, and second, that the impact of both trait and state mindfulness on aggressiveness will be uniquely partially mediated by both anger intensity and anger rumination. 86 participants completed trait measures of mindfulness, anger intensity, and anger rumination, then completed diaries for 35 days assessing mindfulness, anger intensity, anger rumination, anger expression, and self-reported and behavioral aggressiveness. Using multilevel zero-inflated regression, we examined unique contributions of trait and state mindfulness facets to daily anger expression and aggressiveness. We also examined the mediating roles of anger intensity and anger rumination at both trait and state levels. Mindfulness facets predicted anger expression and aggressiveness indirectly through anger rumination after controlling for indirect pathways through anger intensity. Individuals with high or fluctuating aggression may benefit from mindfulness training to reduce both intensity of and rumination on anger

The Rewarding Nature of Provocation-Focused Rumination in Women with Borderline Personality Disorder: A Preliminary fMRI Investigation

Background: Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD. Method: Functional magnetic resonance imaging (fMRI) was utilized to examine this theory in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n = 16). All participants received highly critical feedback on a previously written essay in the scanner, followed by prompts to engage in provocation-focused, self-focused, and neutral thought. Results: Whole-brain analyses showed that in response to the provocation, participants with BPD (compared to controls) demonstrated increased activation in the ventrolateral prefrontal cortex (PFC). BPD participants also showed greater activation in the dorsomedial PFC during provocation-focused rumination (relative to neutral-focus). Subsequent ROI analyses revealed that provocation-focused rumination (compared to neutral-focus) increased activation in the nucleus accumbens for the BPD group only. Conclusions: These findings, while preliminary due to the small sample size and limitations of the protocol, provide initial data consistent with the proposed neurobiological mechanism promoting provocation-focused rumination in BPD. Directions for further research are discussed

Off-World Mental Health:Considerations for the Design of Well-being-Supportive Technologies for Deep Space Exploration

During future long-duration space exploration missions, humans will be exposed to combinations of extreme physical, psychological, and interpersonal demands. These demands create risks for the safety, performance, health, and well-being of both individuals and crew. The communication latency in deep space means that explorers will increasingly have to operate independently and take responsibility for their own self-care and self-management. At present, several research programs are focused on developing and testing digital technologies and countermeasures that support the effective functioning of deep space crews. Although promising, these initiatives have been stimulated mostly by technological opportunity rather than cogent theory. In this perspective, we argue that digital technologies developed for spaceflight should be informed by well-being–supportive design principles and be cognizant of broader conversations around the development and use of digital health applications, especially pertaining to issues of autonomy, privacy, and trust. These issues are important for designing potentially mission-critical health technologies and may be determining factors in the safe and successful completion of future off-world endeavors.publishedVersio

A Cadaveric Study on the Anomalous Origin of Renal and Gonadal Vasculature: An Observational Study

Background: Due to the increasing prevalence of kidney transplantation, a greater awareness of variations in the surrounding vasculature is of surgical importance. During embryological development, both the renal and gonadal arteries arise from lateral mesonephric branches of the dorsal aorta. In adults, gonadal arteries are paired vessels that normally arise from the aorta at the level of the second lumbar vertebra. Methods: Routine cadaveric dissection completed by first-year medical students and dental students incidentally revealed anatomical anomalies. Results: We describe two cadaveric findings in male cases which demonstrate unilateral and bilateral variations of testicular arteries originating from an aberrant renal artery in one case and an accessory renal artery in the other. Conclusion: By increasing awareness of anomalous testicular arteries we hope to encourage the standardization of preoperative vasculature exploration to both minimize intra-operative risk to living male kidney donors and increase patients’ understanding of potential risks and complications prior to consenting to the procedure providing more accurate information prior to surgery

The rewarding nature of provocation-focused rumination in women with borderline personality disorder: a preliminary fMRI investigation

Abstract Background Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD. Method Functional magnetic resonance imaging (fMRI) was utilized to examine this theory in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n = 16). All participants received highly critical feedback on a previously written essay in the scanner, followed by prompts to engage in provocation-focused, self-focused, and neutral thought. Results Whole-brain analyses showed that in response to the provocation, participants with BPD (compared to controls) demonstrated increased activation in the ventrolateral prefrontal cortex (PFC). BPD participants also showed greater activation in the dorsomedial PFC during provocation-focused rumination (relative to neutral-focus). Subsequent ROI analyses revealed that provocation-focused rumination (compared to neutral-focus) increased activation in the nucleus accumbens for the BPD group only. Conclusions These findings, while preliminary due to the small sample size and limitations of the protocol, provide initial data consistent with the proposed neurobiological mechanism promoting provocation-focused rumination in BPD. Directions for further research are discussed

Most viral peptides displayed by class I MHC on infected cells are immunogenic

CD8+ T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8+ T cell responses.This work was supported by a Project Grant from the National Health and Medical Research Council Australia (NHMRC) (APP1084283) (to D.C.T., A.W.P., and N.P.C.); an NHMRC Senior Research Fellowship (APP1104329) (to D.C.T.); an NHMRC Principal Research Fellowship (APP1137739) (to A.W.P.); and a Viertel Fellowship, ARC Future Fellowship, and NHMRC Program Grant (APP1071916) (to N.L.L.G.)

Pichinde virus induces microvascular endothelial cell permeability through the production of nitric oxide

This report is the first to demonstrate infection of human endothelial cells by Pichinde virus (PIC). PIC infection induces an upregulation of the inducible nitric oxide synthase gene; as well as an increase in detectable nitric oxide (NO). PIC induces an increase in permeability in endothelial cell monolayers which can be abrogated at all measured timepoints with the addition of a nitric oxide synthase inhibitor, indicating a role for NO in the alteration of endothelial barrier function. Because NO has shown antiviral activity against some viruses, viral titer was measured after addition of the NO synthase inhibitor and found to have no effect in altering virus load in infected EC. The NO synthase inhibition also has no effect on levels of activated caspases induced by PIC infection. Taken together, these data indicate NO production induced by Pichinde virus infection has a pathogenic effect on endothelial cell monolayer permeability

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited